Patient information: Cushing's syndrome treatment

CUSHING'S SYNDROME OVERVIEW

The treatment of Cushing's syndrome depends upon the underlying cause. Treatment can reverse most of the symptoms of Cushing's syndrome, although this must be done carefully to minimize the possibility of permanent hormone deficiency and treatment side effects.

This article discusses the treatment of Cushing's syndrome. The causes, symptoms, and diagnosis of Cushing's syndrome are discussed separately. (See "Patient information: Cushing's syndrome".) More detailed information about treatment of Cushing's syndrome is also available. (See "Overview of the treatment of Cushing's syndrome".)

MEDICATION-ASSOCIATED CUSHING'S SYNDROME

When Cushing's syndrome is caused by glucocorticoids that are taken for another medical condition, discontinuing the glucocorticoids will resolves symptoms. However, in most cases, the body has adapted to the presence of the glucocorticoids, and they must be tapered off gradually to allow the pituitary and adrenal glands to resume normal function.

Some conditions require prolonged glucocorticoid therapy. In this situation, an alternate plan for managing the signs and symptoms of Cushing's syndrome is necessary.

TREATMENT OF CUSHING'S DISEASE

When Cushing's syndrome results from an ACTH-producing tumor of the pituitary gland (Cushing's disease), treatment may include surgery, radiation, or medication to lower cortisol levels. (See "Primary therapy of Cushing's disease: Transsphenoidal surgery and pituitary irradiation".)

Surgery — Surgical removal of a small, well-defined pituitary adenoma is called transsphenoidal adenomectomy. The pituitary is located at the base of the brain. It is possible to access this area through the gums above the upper front teeth or the nose (figure 1).

Using special instruments, the surgeon makes an incision in one of these areas (figure 2). The incision is extended through the sphenoid sinus, allowing the surgeon to see and remove the adenoma with an endoscope (a thin, lighted tube with a camera). This type of surgery permanently cures Cushing's syndrome in 60 to 70 percent of people.

Sometimes a tumor cannot be identified; in these cases, half of the pituitary gland may be removed (hemihypophysectomy) or 85 to 90 percent of the pituitary gland may be removed (subtotal hypophysectomy) to be certain that the tumor has been removed.

Surgical removal of half or more of the pituitary gland can reduce pituitary function and interfere with ovulation (in women) and sperm production (in men). Lifelong hormone replacement is often necessary after surgery.

Radiation — Radiation can be a useful treatment when pituitary tumors cannot be completely removed by surgery. Radiation of pituitary tumors reduces cortisol levels in about half of adults and most children with Cushing's disease. Because this cortisol-lowering effect takes time (3 to 12 months), medications that lower adrenal cortisol production may be given while waiting for the effects of radiation. These medications include ketoconazole, metyrapone, and aminoglutethimide.

Adrenalectomy — Surgical removal of the adrenal glands (adrenalectomy) is a final measure that may be recommended if other treatments are not successful. Adrenalectomy stops excess cortisol production but requires that you begin lifelong daily glucocorticoid and mineralocorticoid replacement therapy. (See "Patient information: Adrenal insufficiency (Addison's disease)", section on treatment of primary adrenal insufficiency.)

ECTOPIC ACTH SYNDROME

In some people with ACTH-producing, non-pituitary tumors, surgical removal of the tumor eliminates the symptoms of Cushing's syndrome. These tumors are usually in the lung. When complete surgical removal is not possible, treatment with medications that reduce adrenal cortisol production (ketoconazole, metyrapone, and aminoglutethimide) or surgical removal of the adrenal glands (adrenalectomy) may be necessary to lower cortisol levels.

ADRENAL GLAND TUMORS

Adrenal tumors are usually treated with surgical removal of the affected adrenal gland, leaving the opposite adrenal gland for cortisol production. If the tumor is an adenoma (a benign tumor), surgery always cures the associated Cushing's syndrome.

If the tumor is a carcinoma (a cancerous tumor), surgery is the only way to cure the cancer; radiation, chemotherapy, and treatment with mitotane (a medication that is toxic to cortisol-producing cells) are usually required to lower cortisol levels. After these treatments, daily adrenal hormone replacement is usually necessary. (See "Patient information: Adrenal insufficiency (Addison's disease)", section on treatment of primary adrenal insufficiency.)

NODULAR ADRENAL HYPERPLASIA

Treatment of nodular adrenal hyperplasia usually requires surgical removal of both adrenal glands. Before surgery, medications that inhibit adrenal enzymes (ketoconazole, metyrapone, or aminoglutethimide) can lower cortisol levels.

After surgery, daily adrenal hormone replacement is usually necessary. (See "Patient information: Adrenal insufficiency (Addison's disease)", section on treatment of primary adrenal insufficiency.)

CUSHING'S SYNDROME DURING PREGNANCY

Cushing's syndrome is rare during pregnancy. The excess cortisol production is usually caused by an adrenal tumor, most often an adenoma (a benign tumor), although some patients have a pituitary tumor (Cushing's disease). (See "Cushing's syndrome in pregnancy".)

Although most of the excess cortisol does not cross the placenta and affect the fetus, untreated Cushing's syndrome poses a risk to pregnant women because it can lead to maternal complications such as high blood pressure and gestational diabetes, and it is associated with miscarriage and premature delivery.

When Cushing's syndrome is caused by an adrenal tumor or a benign pituitary tumor (Cushing's disease), surgical removal of the adrenal or pituitary gland can lower the abnormal cortisol levels without affecting the pregnancy.

EFFECTIVENESS OF CUSHING'S SYNDROME TREATMENT

If treatment removes the source of excess cortisol, most of the symptoms of Cushing's syndrome disappear within 2 to 12 months. Osteoporosis begins to improve within six months and continues to improve over several years. With successful treatment, children with Cushing's syndrome can regain much of their lost bone density and growth. Some high blood pressure and glucose intolerance may persist. Although psychiatric symptoms usually improve, some conditions can linger even after cortisol levels have been lowered.

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Cushing's syndrome
Patient information: Adrenal insufficiency (Addison's disease)

Professional Level Information:
Causes and pathophysiology of Cushing's syndrome
Clinical manifestations of Cushing's syndrome
Cushing's syndrome due to ACTH-independent macronodular adrenal hyperplasia
Cushing's syndrome in pregnancy
Dexamethasone suppression tests
Establishing the cause of Cushing's syndrome
Establishing the diagnosis of Cushing's syndrome
Overview of the treatment of Cushing's syndrome
Primary therapy of Cushing's disease: Transsphenoidal surgery and pituitary irradiation
Treatment of Cushing's syndrome: Diminishing adrenal cortisol synthesis

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• National Library of Medicine

      (www.nlm.nih.gov/medlineplus/healthtopics.html)

• The Hormone Foundation

      (www.hormone.org/public/other.cfm, available in English, Spanish, and Portuguese)

• National Institute of Diabetes and Digestive and Kidney Diseases

      (http://endocrine.niddk.nih.gov/index.htm)

• National Adrenal Diseases Foundation

      (516) 487-4992
      (www.nadf.us)

• Pituitary Tumor Network Association

      (www.pituitary.org)

• Cushing's Support & Research Foundation

      (617) 723-3674
      (www.csrf.net/)

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